We are applying quantitative cytochemical methods to the study of bladder tumor development in Fisher rats fed N-butyl-N-(4-hydroxybutyl)-nitrosamine. This study will further understanding of the basic biological steps in bladder tumor progression and may provide a cytochemical foundation for improvements in exfoliated cell diagnostic cytology. Our attention is focused on characterizing the early cellular changes in tumors. The temporal acquisition of cytochemical changes is being related to carcinogen protocol, bladder pathology, conventional diagnostic cytology, and electron microscopic observations. Quantitative cytochemical measurements of cell size, DNA content, protein content, and protease, esterase, and dehydrogenase activities are being made. Measurements of fluorescence and absorbtion are made using static cytometers and flow fluorocytometers as appropriate.